Meta-Analysis of DNA Methylation and Expression in Liver Cancer Patients

Hepatocellular carcinoma (HCC), the most common liver cancer, is the second leading cause of cancer-related death worldwide. HCC is often diagnosed at late stages, for which there are no effective chemotherapies. Biomarkers unique to HCC patients could be used to detect HCC early and improve treatment. In the present project, we have performed a meta-analysis to compare the gene-specific DNA methylation and gene expression patterns of HCC patients as reported by four independent studies. Our goal was to discover the strongest changes that distinguish HCC from normal tissue. The relationship between methylation and expression in HCC was examined and genes epigenetically regulated in HCC were identified. The top changes within genes, gene families and pathways could be of interest in further investigations of potential HCC biomarkers. A significant correlation between DNA hypomethylation and gene activation and between DNA hypermethylation and gene silencing was found. CpG islands, commonly found in promoter regions, are predominantly hypermethylated in HCC, while CpGs outside of CpG islands are predominantly hypomethylated in gene bodies. 149 genes were found to be significantly differentially methylated between tumors and normal adjacent tissue, and 169 genes were found to be significantly differentially expressed. Genes identified for further research are GNG7, WNT5B, RXRG, HOXB7, and SMARCB1. No overlap was found between differentially expressed and methylated genes. Nevertheless, common gene families and pathways were identified where more potential biomarkers could be found in future studies

Epstein-Barr virus (EBV) infection in B-cell non-Hodgkin's lymphomas in children: virus latency and its correlation with CD21 and CD23 molecules.

Epstein Barr virus (EBV) infection of human B lymphocytes in vitro results in immortalisation of the cells and augmented membranous expression of numerous B-cell activation molecules, including CD23. Other studies demonstrated that only those B lymphocytes which carry the surface CD21 (EBV receptor) become transformation-competent. Inspired by the relatively unclear relations between expression of EBV and those of CD21 and CD23 in in vivo conditions we have decided to define correlations between tissue markers of EBV and of CD21 and CD23 molecules in B-cell non-Hodgkin's lymphomas (NHLs) in children. The studies were performed on an archival tissue material originating from children with B-cell NHLs (n=26) using immunocytochemical techniques, in situ hybridisation, and PCR. Our studies confirmed the latent phase of EBV infection in all of the EBV-positive patients. Viral proteins as well as viral RNAs (EBERs) was found both in the cytoplasm, in cell nuclei and in cell membranes of mainly the transformed lymphocytes B. Expression of the latent proteins (EBNA2 and LMP1) and that of EBERs in B-cell NHLs was significantly higher as compared to children with nonneoplastic lesions. The studies demonstrated reciprocally positive correlations between expressions of CD21 and CD23 in our children, but no correlation could be demonstrated between expression of EBV tissue markers and that of CD21 and/or CD23. Positive correlation was confirmed between expression of EBNA2 and LMP1 as well as between expression of the two proteins and EBERs in B-cell NHLs. Our studies have shown mainly latency III pattern of EBV. We have also demonstrated a novel form of EBV latency with no EBERs expression. The high detectability of EBV-positive cases both in the group of B-cell NHLs (77%), and in the group with non-neoplastic lesions (64%) suggested that only more pronounced tissue expression of EBV markers in B-cell NHLs as compared to the non-neoplastic material may point to a potential role of EBV in pathogenesis of lymphoma in this group of population in our country

Assessment of cardiac function in donor and recipient fetuses during a 7-day follow-up after selective laser photocoagulation of communicating vessels due to TTTS

Objectives: The aim of the study was to analyze the changes in cardiac function and myocardial contractility of donor and recipient fetuses with twin-to-twin transfusion syndrome (TTTS) subjected to selective laser photocoagulation of the communicating vessels (SLPCV), between and after the procedure. Finally, we verified if fetuses with Quintero’s stage I TTTS presented with early impairment of myocardial contractility.  Material and methods: We selected 77 consecutive women with twin pregnancies, whose both fetuses survived at least seven days post-SLPCV. Myocardial contractility of both fetuses was evaluated ultrasonographically, and their myocardial performance indices (Tei-Index values) and shortening fractions (SF) were determined.  Results: In donor fetuses, the Tei-Index values for both right and left ventricle remained within the respective reference ranges both before the procedure and during a 7-day follow-up. A significant change in shortening fraction values for the left ventricle in recipient fetuses and the right ventricle of in the donors was observed during a 7-day follow-up.  Conclusions: Comparison of the cardiac parameters of donors and recipients revealed significant differences in Tei-indices during the entire follow-up period.  The group with Quintero’s I stage TTTS included 74% of recipient fetuses with abnormal Tei-Index values for the right ventricle (mean 0.53).

Perinatal and neonatal outcome in patients with preeclampsia

Objectives: Preeclampsia (PE) affects 2–5% of pregnant women. Hypertensive disorders of pregnancy are associated with adverse maternal and perinatal outcomes. Material and methods: This study included 88 women showing gestational hypertension (GH) or PE symptoms, and their newborns. Results: The rate of FGR was 43% for mothers with PE, compared to 8% with GH. The association was significant, p = < 0.001 but with moderate strength, Cramer’s V = 0.40. The risk of FGR increased nine times when PE occurred, as the odds ratio was 9.25 (CI: 2.46–34.83), p = 0.001. PE was associated with FGR risk if delivery time was less than 34 weeks compared to a delivery time of more than 34 weeks. This was 82% of FGR cases for < 34 weeks, compared with 35% of cases in > 34 group, (p = 0.001; Cramer’s V = 0.50). PE was also associated (p = 0.01, Cramer’s V = 0.27) with the type of delivery, as the caesarean section rate was 74%, compared to 50% in the GH group. This made it three times higher the likelihood of delivery by caesarean section, as the odds ratio was 3.10 (CI: 1.24–7.75), p=0,02. Delivery time was significantly (p < 0.001) shortened to 38 weeks (27–41), compared to 40 weeks (38–42) GH mothers. There was no distinction in median age for PE and GH mothers (p = 0.124). The overall clinical status of neonates was proportional despite the mother’s PE. The sum of Apgar points in the first, and then the second to third minute, did not differ significantly, p = 0.370 and 0.560, respectively. The number of peripheral blood platelets and leucocytes was not reduced (p = 0.821 and 0.534) in infants when the mother suffered from PE. Conclusions: The prediction of adverse maternal outcomes from hypertensive diseases of pregnancy is key to optimal management, including the timing of delivery and planning for the most appropriate place of care.

Intrauterine deaths — an unsolved problem in Polish perinatology

Objectives: The Polish criteria for “intrauterine death” include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered. Material and methods: An analysis using 142,662 births in the period between 2015–2020 in 11 living in Poland. The first subgroup was admitted as patients > 22 to the beginning of the 30th week of pregnancy (n = 229), and the second from the 30th week of pregnancy inclusively (n = 179). In the case of women from both subgroups, there was a risk of preterm delivery close to hospitalization. Results: It was found that stillbirth in 41% of women in the first pregnancy. For the patient, stillbirth was also the first in his life. The average stillbirth weight was 1487 g, the average body length was 40 cm. Among fetuses up to 30 weeks, male fetuses are born more often, in subgroup II, the sex of the child was usually female. Most fetal deaths occur in mothers < 15 and > 45 years of age. Conclusions: According to the Polish results of the origin of full-term fetuses > 30 weeks of gestation for death in the concomitant antenatal, such as placental-umbilical and fetal hypoxia, acute intrapartum effects rarely, and moreover < 30 Hbd fetal growth restriction (FGR), occurring placental-umbilical, acute intrapartum often